Sunday, February 12, 2017

Can drug be approved without demonstrating efficacy?

Pharmaceutical industry is assessing the impact of the Trump
administration on regulations in drug approval and drug price. It looks like
there will be some government intervention on the drug price after all. It is
also likely to have some changes in drug approval process, primarily through
the reform in FDA.

There have been a lot of buzz around the Trump’s choice for
new FDA commissioner. The choice of the new FDA commissioner could be a signal
for the future direction in drug regulation. The most discussed candidate
is Jim O’Neill and the most discussed topic is his view about the drug approval
without efficacy.

“...another great, probably better idea is progressive
licensing. We should reform the FDA so that there is an approving drug after the
sponsor has demonstrated the safety. Let
people start to use them at their own risk, but not much on the safety. Let
demonstrate the efficacy after it has been legalized.”

It is true that FDA may have some bureaucratic practices and
has become the roadblock to the drug approval process. A lot of times, FDA is
too conservative and too cautious in approving the drugs, this is obvious ever since
the Vioxx incidence. Whenever there is any uncertainty (in both safety or efficacy), FDA will rather kill
(not approve) a new product. In this way, nobody will blame them for approving
an unsafe drug or a drug that is not efficacious. Exceptions are some
cases where FDA reluctantly approved the drug because of the pressures from
outside (for example, the
female Viagra for HSDD
in 2015 and eteplirsen for Duchenne Muscular Dystrophy in 2016).

It is likely that FDA reform is needed to cut bureaucratic
red tape that slows the progress of science, reduce the time and cost for
bringing the next generation of drugs to the market. However, approving a drug
without demonstrating the efficacy (with demonstrating only the safety) will
not work. It is jumping from one extreme to another.

Secondly, if a drug can be marketed without demonstrating
the efficacy, the market will be full of the products like the ‘snake oil’ – no
harm, but no effect. Wonder who will pay for the cost of these drugs in an era that the health insurance cost has come almost unmanageable?

Thirdly, the safety assessment is usually full of the
subjective component in it. The same safety signal could be viewed as critical by
some and as not critical or trivial by others. Recently, a new antibiotics, Solithromycin,was not approved by FDA because the data from the pivotal clinical trials
indicated more subjects in Solithromycin group had ALT/AST elevations than the
control group. However, this imbalance in ATL/AST elevations could be viewed as
not critical because the elevations were transient and disappeared after the
use antibiotics was stopped. Considering that the use of solithromycin is
usually short-term, the risk for solithromycin causing the liver damage can be
viewed as a manageable risk. However, FDA declined the approval of
solithromycin anyway even at the time that fighting the antibiotics resistant infections was so critical.

My wishful thinking is that FDA will be reformed to speed up
the drug approval process by removing some of the regulations, but not go to
another extreme to approve a drug without demonstrating the efficacy. To
protect the safety of the American people, the clinical trial and drug approval
process will remain highly regulated. Even with FDA reform that causes significant
reduction in developing time and cost, it will still be a lot more than
developing a software.